Pharmaceutical Sciences Faculty Publications
Urinary Estrogens and Estrogen Metabolites and Subsequent Risk of Breast Cancer Among Premenopausal Women
Document Type
Article
Publication Date
2-1-2012
Journal Title
Cancer Research
ISSN
1538-7445
Volume
72
Issue
3
First Page
696
Last Page
706
DOI
10.1158/0008-5472.CAN-11-2507
PubMed ID
22144471
PubMed Central® ID
PMC3271178
Abstract
Endogenous estrogens and estrogen metabolism are hypothesized to be associated with premenopausal breast cancer risk but evidence is limited. We examined 15 urinary estrogens/estrogen metabolites and breast cancer risk among premenopausal women in a case-control study nested within the Nurses' Health Study II (NHSII). From 1996 to 1999, urine was collected from 18,521 women during the mid-luteal menstrual phase. Breast cancer cases (N = 247) diagnosed between collection and June 2005 were matched to two controls each (N = 485). Urinary estrogen metabolites were measured by liquid chromatography-tandem mass spectrometry and adjusted for creatinine level. Relative risks (RR) and 95% confidence intervals (CI) were estimated by multivariate conditional logistic regression. Higher urinary estrone and estradiol levels were strongly significantly associated with lower risk (top vs. bottom quartile RR: estrone = 0.52; 95% CI, 0.30-0.88; estradiol = 0.51; 95% CI, 0.30-0.86). Generally inverse, although nonsignificant, patterns also were observed with 2- and 4-hydroxylation pathway estrogen metabolites. Inverse associations generally were not observed with 16-pathway estrogen metabolites and a significant positive association was observed with 17-epiestriol (top vs. bottom quartile RR = 1.74; 95% CI, 1.08-2.81; P(trend) = 0.01). In addition, there was a significant increased risk with higher 16-pathway/parent estrogen metabolite ratio (comparable RR = 1.61; 95% CI, 0.99-2.62; P(trend) = 0.04). Other pathway ratios were not significantly associated with risk except parent estrogen metabolites/non-parent estrogen metabolites (comparable RR = 0.58; 95% CI, 0.35-0.96; P(trend) = 0.03). These data suggest that most mid-luteal urinary estrogen metabolite concentrations are not positively associated with breast cancer risk among premenopausal women. The inverse associations with parent estrogen metabolites and the parent estrogen metabolite/non-parent estrogen metabolite ratio suggest that women with higher urinary excretion of parent estrogens are at lower risk.
Keywords
Breast neoplasms, case-control studies, cell transformation, neoplastic, chromatography, liquid, estrogens, premenopause, tandem mass spectrometry
Recommended Citation
Eliassen, A. Heather; Spiegelman, Donna; Xu, Xia; Keefer, Larry K.; Veenstra, Timothy D.; Barbieri, Robert L.; Willett, Walter C.; Hankinson, Susan E.; and Ziegler, Regina G., "Urinary Estrogens and Estrogen Metabolites and Subsequent Risk of Breast Cancer Among Premenopausal Women" (2012). Pharmaceutical Sciences Faculty Publications. 237.
https://digitalcommons.cedarville.edu/pharmaceutical_sciences_publications/237